tbuckley/cabot-search huggingface dataset:
Characteristics of long-term survivors with EGFR mutant (EGFRm) metastatic non-small cell lung cancer (mNSCLC).
Authors: Melina Elpi Marmarelis, Connor B. Grady, Caroline McCoach, Fangdi Sun, Geoffrey Liu, Devalben Patel, Jorge J. Nieva, Kristen A. Marrone, Vamsidhar Velcheti, Stephen V. Liu, Tejas Patil, Jared Weiss, William Schwartzman, Liza C Villaruz, Amanda Cass, Dara L. Aisner, Wei-Ting Hwang, Charu Aggarwal, D. Ross Camidge, Lova Sun
Journal: Journal of Clinical Oncology (2023)

9116 Background: Although osimertinib has become standard first-line (1L) therapy for patients (pts) with EGFRm mNSCLC, a subset treated with earlier-generation EGFR-targeted TKIs and chemotherapy have had long-term survival. We sought to characterize clinical features of long-term survival in pts with EGFRm mNSCLC treated prior to the osimertinib era. Methods: Data were abstracted from electronic medical records at 12 cancer centers participating in the Academic Thoracic Oncology Medical Investigator’s Consortium (ATOMIC). We included patients with mNSCLC with sensitizing mutations in EGFR who started 1L systemic therapy before 2015. Survival distributions and predictors were assessed using Kaplan-Meier estimates and a multivariable Cox proportional hazards model including time-dependent brain metastasis (met) development, age, 1L therapy (targeted vs. chemotherapy), sex, race, and smoking status. Multivariable logistic regression was used to evaluate baseline predictors associated with 5+ year survival vs. not for those with known survival status at 5 years after start of 1L. Results: We identified 304 patients (69% female, 56% White, 29% Asian, mean age 61.2). First-line targeted therapy was given in 70% of patients. With a median follow-up of 81.5 months, median overall survival was 63.5 months (95% CI 59.4-71.9). 135 (44%) pts survived 5+ years; among those with baseline next-generation sequencing (NGS), presence of a baseline pathogenic ERBB2 variant was higher in 5+ year survivors (4/51 [8%], 2x amplification, y772_A775dup, S310F) v others (1/65 [2%], amplification). Among 161 pts with baseline brain imaging, both baseline and on-treatment development of brain mets were associated with worse survival (HR 1.29, 95% CI 1.21-1.37; HR 1.59, 95% CI 1.47-1.72; both P &lt; 0.001). Excluding 22 patients lost to follow-up before 5 years, a history of smoking (OR 2.99, 95% CI 1.35-6.90, P = 0.008) and baseline brain metastases (OR 3.57, 95% CI 1.64-8.13, P = 0.002) were associated with death before 5 years. Conclusions: Long-term survivors with EGFRm mNSCLC treated before the osimertinib era were more likely to be nonsmokers and have no baseline brain metastases. This highlights a subset of EGFRm patients who had excellent outcomes with older treatment strategies and may not benefit as much from intensification approaches. Additional baseline mutational data will be presented at the conference.
Inverse association of post-transplant malignancy and graft failure on survival outcome following double lung transplantation.
Authors: Jeeyeon Lee, Hye Sung Kim, Yunjoo Lee, Liam Il-Young Chung, Won Jun Yang, Jisang Yu, Ankit Bharat, Young Kwang Chae
Journal: Journal of Clinical Oncology (2023)

10629 Background: Graft failure (GF) and post-transplant malignancy (PTM) are common causes of death in lung transplantation. Immunosuppression to prevent graft failure is known to lead to de novo malignancies after solid organ transplantation. Here, we assess the relationship between graft failure and de novo malignancies after double lung transplantation (DLT). Methods: Data extracted from the Organ Procurement Transplantation Network (OPTN) registry were analyzed. DLT cases for non-cancerous diseases were selected. We evaluated the overall survival (OS) of recipients with or without PTM (PTM+ or PTM-), and that of recipients with or without GF (GF+ or GF-) after DLT. The association between GF and PTM was investigated. Results: Among 23,935 DLT recipients, there were 5,629 cases (23.5%) of PTM+ and 18,306 cases (76.5%) of PTM -, and 2,316 cases (9.7%) of GF+ and 21,619 cases (90.3%) of GF- following DLT. Among GF+ cases, the prevalence of acute, hyperacute, and chronic rejection after DLT was 1,962 cases (84.7%). The OS in recipients with GF+ was worse than that in recipients with GF- (p &lt; 0.001). However, inversely, the OS in recipients with PTM+ was better than that of recipients with PTM- (p &lt; 0.001). When patients were categorized into four categories by each factor (GF-, GF+, PTM+, PTM-), the GF rate was lower in recipients with PTM+ than in those with PTM- [GF+/PTM+ (n = 368, 1.5%) versus GF+/PTM- (n = 1,948, 8.1%)] (p &lt; 0.001), and the PTM+ rate was higher in recipients with GF- than in those with GF+ [GF-/PTM+ (n = 5,261, 22.0%) versus GF+/PTM+ (n = 368, 1.5%)] (p &lt; 0.001). And the GF-/PTM+ group showed the best prognosis with 97.3 months of median OS, and the GF+/PTM- group showed the worst prognosis with 36.8 months of median OS (p &lt; 0.001). Conclusions: Recipients who developed PTM following DLT had longer OS compared with those who did not. And the GF rate was significantly lower in recipients with PTM compared to those without PTM. Further research is needed to investigate the underlying mechanism of the inverse association between PTM and GF in DLT recipients.
Patterns of care delivery and outcomes in patients with melanoma brain metastases treated with ipilimumab/nivolumab.
Authors: Tarek Haykal, Michelle Ferreira, Melissa Lowe, Brent Allen Hanks, Peter E. Fecci, John P. Kirkpatrick, Eugene John Vaios, Zach Reitman, April K.S. Salama
Journal: Journal of Clinical Oncology (2023)

e21510 Background: Patients (Pts) with metastatic melanoma presenting with brain metastases (MBM) have a high morbidity and mortality risk. The combination of ipilimumab/nivolumab (I/N) has demonstrated high intracranial response rates in selected, asymptomatic pts, suggesting there is a subset of pts who may be able to forgo or delay intracranial therapies. There is currently limited real world data on how many pts with MBM are successfully treated with this approach. We sought to explore our clinical experience at Duke University with combination immune checkpoint inhibitors for pts with MBM. Methods: An electronic database search was conducted for all metastatic melanoma pts treated with PD-1 therapies between 2015 and 2021. Pts treated with combination ICIs for brain metastases were included. The primary outcome was overall survival (OS). Secondary outcomes were need for local therapies (radiation (RT): stereotactic radiosurgery or whole brain radiation therapy or craniotomy), and immune related adverse events (irAEs). Results: Between 2015 and 2021, 66 pts with MBM received I/N, with a median follow-up of 30.4 months. Median age was 68, 60.6% were male and 61% had a BRAF mutation. 38 pts were asymptomatic. Of the 28 symptomatic patients 61% were on corticosteroids at the time of I/N initiation. 56% of pts received local therapy prior to start of I/N, 17% during and 18% after discontinuing I/N. 53% of pts were initiated on I/N as first line systemic therapy for MBM. 56% of patients had to discontinue I/N after one cycle because of high-grade irAEs. 13.8% of patients that received RT to the brain developed radionecrosis. Median OS was 25.6 months in the overall cohort, with a 1 year OS of 63%. There was a trend towards a higher risk of death for symptomatic versus asymptomatic patients HR:1.96 [95% CI: 0.96, 3.97; P:0.06]. Of the 38 asymptomatic patients, only 6 patients did not receive local therapies with either RT or craniotomy. Two of these patients died from melanoma progression, one from intra-cranial progression, the other from both intra-cranial and extra-cranial progression, and 4 remain alive without evidence of progression. Conclusions: The majority of pts with MBM are ultimately treated with multimodality therapy. Advances in systemic therapies have provided meaningful clinical benefit that could allow a limited number of asymptomatic patients to forgo local therapy, but currently few pts are treated in this manner.
External validation of the Molecular International Prognostic Scoring System (IPSS-M) for myelodysplastic syndromes.
Authors: Brian Chernak, Abdullah Ali, Amna Jan, Sanjay Mukherjee, Joseph G. Jurcic, Azra Raza
Journal: Journal of Clinical Oncology (2023)

7056 Background: Myelodysplastic Syndromes (MDS) comprise of a group of clonal diseases characterized by dysplastic hematopoietic progenitor cells, leading to cytopenias and in select cases transformation to acute myeloid leukemia (AML). In June 2022 the Molecular International Prognostic Scoring System (IPSS-M) was developed to build on the traditional IPSS-R and is reported to be prognostic even with incomplete molecular data. We aimed to validate this scoring system with an external dataset, and utilize a patient population which typically does not contain complete molecular testing at diagnosis. Methods: This single center study at a tertiary medical center in New York, NY was conducted as an external validation of the IPSS-M. Patients with MDS who had documented peripheral blood counts, bone marrow biopsies, and cytogenetic data were identified in the institutional tissue bank. After eliminating repetitive patient samples, 405 patient entries, collected between July 7, 2010 and March 29, 2022 were included in this study. 392 patients had previously been categorized by IPSS-R score. 332 patients had at least one subsequent follow-up event. 94 patients had bone marrow biopsies that were peri-diagnostic (within 12 months of diagnosis). Results: Patients in the entire cohort had a median age of 74 years (range, 30-96). The median follow-up duration was 1.5 years (range 0.0-9.9 years). Nearly all patients had at least partial molecular diagnostic data. Other than PRPF8 mutations (0%), all other mutations included in the IPSS-M scoring system were tested in a subset of the study population. The most common mutations in the patient population were SF3B1 (20.4%), ASXL1 (17.6%), and SRSF2 (15.9%); 12.2% of patients had the del5q cytogenetic abnormality, and 5.6% were found to have at least one TP53 mutation; 2.7% were TP53 (multi-hit). 29% of all patients were up-staged from IPSS-R to IPSS-M score, while 12% were down-staged. At the time of study evaluation, there were 84 events; 61.3% of patients were alive at the time of analysis. The median overall survival was 3.6 years (25-75% range: 2.75-5.50 years). When limited to patients with peri-diagnostic bone marrow biopsies, there were statistically significant differences in overall survival between IPSS-M categories (p&lt;0.000001) as well as IPSS-R categories (p&lt;0.00001). There was no statistical difference in survival between IPSS-M categories (p=0.6) or IPSS-R categories (p = 0.2) if scores were calculated at any time point in the patient’s disease course. Conclusions: This study validates the utility of both the IPSS-M and the IPSS-R scoring systems, and notably retains important risk stratification with incomplete diagnostic data. Importantly, the scoring systems are not effectively prognostic as the disease progresses, and thus should only be utilized at or near the time of diagnosis.
Differential therapeutic benefit of platinum-doublet chemotherapies with ICIs based on the classification by combined with smoking status and PD-L1 expression in patients with advanced NSCLC.
Authors: Akito Fukuda, Tatsuya Yoshida, Ken Masuda, Yuki Shinno, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Yuichiro Ohe
Journal: Journal of Clinical Oncology (2023)

e21131 Background: Chemotherapy combined with immune checkpoint inhibitors (Chemo-ICIs) has been the standard of care for advanced NSCLC patients. Smoking status is associated with PD-L1 expression and the TILs within tumor microenvironment, which leads to the efficacy of ICIs. It remains unclear how the combined with PD-L1 expression and smoking status affect the efficacy of Chemo-ICIs. Methods: We retrospectively reviewed advanced NSCLC patients without driver mutation (EGFR, ALK, ROS-1, BRAF) who received Chemo-ICIs from January 2019 to June 2021, and Chemo from January 2014 to December 2016 as a first-line therapy at the National Cancer Center Hospital, Tokyo, Japan. The additional benefit of ICIs to chemotherapy were evaluated by comparing the Chemo-ICIs group with Chemo group. Results: During study period, 225 patients received Chemo-ICIs and 133 received Chemo as a first line therapy. Overall response rate (ORR) and progression free survival (PFS) was significantly better in the Chemo-ICIs group than the Chemo group (ORR: 44.9% vs. 40.2%, p=0.01, and median PFS: 8.2 months vs. 6.2 months, P&lt;0.001). The median overall survival was 27.9 months in Chemo-ICIs and 20.4 months in chemo (P=0.14). In the subgroup analysis of PFS, the benefit of Chemo-ICIs compared to Chemo was not observed in never-smoker patients (8.9months vs 8.8months, P=0.27). In contrast, among smoker patients, Chemo-ICIs showed significant longer PFS compared to Chemo (7.5 months vs 5.7 months, P&lt;0.001). Next, patients received Chemo-ICIs were classified into six groups, based on the smoking status (never smoker or smoker) and PD-L1 expression (TPS: 0%, 1-49%, or 50%). Chemo-ICIs showed better PFS rate at 12 months in the smoker/ TPS ≥50% group (42.2% vs 25.0%, p=0.03), and the never smoker/TPS ≥50% group (75.0% vs 27.3%, p=0.05) compared with Chemo (Table). In patients with 1-49% TPS, compared to the Chemo group, significant PFS benefit of ICIs was observed only in smoker patients (42.2% vs 25.0%, p=0.003), not in never smoker patients (46.2% vs 27.3%, p=0.13). In patients with 0% TPS, although the additional benefit of ICIs to Chemo was not observed both in never and smoker patients, PFS rate at 12 months in never smoker (13.3%) was lowest among all six groups. Conclusions: Our study suggested that additional benefit of ICIs to chemotherapy could be predicted by combined with smoking status and PD-L1 expression.[Table: see text]
The COVID-19 pandemic's impact on diagnosis of cancers detectable through screening.
Authors: Carmen Guerra, Peter Edward Gabriel, Abigail Doucette, Colleen M Grosso, Armenta L. Washington, Emily Verderame, Claudia Melendez, Christina Wooden, Daniel Lee, Linda White Nunes, Christine E Edmonds, Brian S. Englander, Roderick Brathwaite, Michael Noji, Erin E. Hollander, Jaia Wingard, Farouk Dako, Corrine Rhodes, Shivan Mehta, Robert H. Vonderheide
Journal: Journal of Clinical Oncology (2023)

e18669 Background: The COVID-19 pandemic caused major disruptions in cancer screenings. The delays in screenings were expected to be more pronounced in racial minorities due to their pre-existing barriers to accessing cancer screenings and care. Starting in 2020, to mitigate those expected declines in cancer screenings among Black individuals, the Abramson Cancer Center (ACC) and Penn Medicine decentralized cancer screenings using mailed and drive-through Fecal Immunochemical Testing, mobile mammography, community PSA blood testing and lung cancer risk assessments. Methods: The ACC catchment area comprises more than 7 million individuals who reside primarily in 12 counties across the three states (PA, NJ, DE) surrounding Philadelphia. We used the ACC cancer registry to review the number of analytic cases for cancer diagnoses for which screening is available during the three years before and two years since the pandemic began. We compared the proportion of cancer cases diagnosed in Black patients seeking treatment at the ACC throughout all five years. Results: A total of 16.5% of the individuals diagnosed and treated for cancer from 2017-2021 at ACC were Black. In 2020, there was a decline in the number of analytic cases of breast, cervical, colorectal, lung and prostate cancer at the ACC, but by 2021, the number these cancer cases returned to pre-pandemic levels. Compared to pre-pandemic years, the proportion of Black patients with these cancers was unchanged in 2020 for all cancers except for cervical and colorectal cancer which increased by almost 2%. Conclusions: During the pandemic, there was a temporary decline in the number of ACC patients diagnosed with cancers for which a screening test is available, suggesting a correlation with the disruptions in cancer screenings caused by the pandemic. The declines in cancers diagnosed did not disproportionately impact Black individuals with the exception of cervical and colorectal cancer where there was a slight increase. Limitations include the small number of cervical cancer analytic cases which may prevent reliable estimates. Decentralization of cancer screenings for Black communities during the pandemic may have mitigated potential delays to accessing timely cancer screenings. [Table: see text]
Quality of life in patients diagnosed and treated for breast cancer in Uruguay.
Authors: Natalia Camejo, Dahiana Amarillo, Cecilia Castillo, Maria Guerrina, Florencia Savio, Mariana Carrasco, Noelia Strazzarino, Ana Laura Hernandez, Guadalupe Herrera, Gabriel David Krygier
Journal: Journal of Clinical Oncology (2023)

e24096 Background: Breast cancer (BC) and its treatment can impair patient quality of life (QoL), and those undergoing more aggressive treatments may be more severely impacted. Objective: Assess the level of perception of the QoL of patients treated for BC at the Hospital de Clínicas and the Departmental Hospital of Soriano. Methods: A questionnaire for cancer patients (EORTC, QLQ-C30) and one specific for BC (EORTC QLQ-BR23) were used. Results: A total of 158 patients who had completed chemotherapy treatment at least one year prior to the evaluation were enrolled. The average age was 61 years old. QLQ-C30 questionnaire: the global QoL score (GQOL) was high: 70.9. Patients undergoing breast-conservation surgery (BCS) had better scores in physical and emotional functioning (p &lt; 0.005) and presented less frequently with: pain, constipation and financial difficulties (p &lt; 0.005). Those undergoing sentinel lymph node biopsy (SLNB) had higher scores for GQOL and for physical, role and social functioning scales (p &lt; 0.001) and had less fatigue, pain, insomnia and financial difficulties (p &lt; 0.005). Questionnaire QLQ-BR23: sexual functioning and sexual enjoyment scales were relatively low. Patients undergoing BCS had better scores on the functional scales: body image and future outlook; and fewer breast symptoms (p &lt; 0.005). Those undergoing SLNB also had better scores on the functional scales for body image and future outlook future and presented less frequently with symptoms (p &lt; 0.005). Conclusions: Patients had high values on the GQOL scale, those undergoing BCS and SLNB had better scores on most functional and problem/symptom scales. The implementation of intervention strategies aimed at improving the quality of life and the physical and emotional care of patients is recommended. Uruguayan BC patients experience high values on the GQOL scale, those undergoing BCS and SLNB had better scores on most functional and problem/symptom scales. Patients undergoing BCS had better scores in physical and emotional functioning and presented less frequently with: pain, constipation and financial difficulties. With respect to the type of axillary surgery received, patients who underwent SLNB had higher scores on the GQOL scale and on the physical, role and social functional scales. The implementation of intervention strategies aimed at improving the quality of life and the physical and emotional care of patients is recommended.
Incidence of solid malignancies (SM) among patients with Waldenström macroglobulinemia (WM): Analysis of the SEER database (2000-2019).
Authors: Alankrita Taneja, Rahul Mishra, Sumukh Arun Kumar, Ajay Iyer, Jens Hillengass
Journal: Journal of Clinical Oncology (2023)

e18902 Background: WM is an indolent disease with a median survival of ~ 16 years following diagnosis. We aimed to study the incidence of various SM among patients with WM, which can help in their targeted surveillance. Methods: We used SEER 17 registry to identify adult [ &gt; 20 years(y)] patients(pts) with an index diagnosis (dx) of WM between 2000- 2019. We included ICD-O-3 codes 9671/3 (Lymphoplasmacytic lymphoma) and 9761/ (Waldenstrom macroglobulinemia) to identify index dx. Only first of the two codes was used if both were mentioned for same pt. Pts were grouped based on age at WM dx ≤60y (young) and &gt; 60y (old) for analysis. We used ICD-O-3/WHO 2008 codes assigned to site of SM to identify subsequent diagnosis ( &gt; 2months after index diagnosis) of SM. We included the first SM site, for pts with &gt; 1 subsequent SM. We analyzed SM sites with &gt; 15 patients. We excluded patients with diagnosis made from death certificate or autopsy. Follow up period was till December 2019. Demographics and treatment details were extracted using SEER Stat v 8.4.0.1 software. Statistical analyses were performed using R 4.2.2. Chi-squared test was used to calculate difference between categorical variables. Kaplan Meier method and log rank test were used to estimate overall survival (OS). Results: We identified 8099 patients with a dx of WM, of which 794 (9.8%) had subsequent SM. WM and SM were diagnosed at median (IQR) ages of 70 (62-76)y and 74 (67-81)y, with a median gap of 41 (20-79) months. Majority of WM survivors with SM were males (517/794, 65.1%), white (91.4%) and old ( &gt; 60y) (79.2%) at WM diagnosis. Ten SM sites, each with &gt; 15 pts were identified (Table). Most common site of SM in young WM females was breast, while it was lung and bronchus(LB) in the older group. In males, prostate, and LB were two most common sites in each age-groups. 1% of older male patients developed breast cancer. (Table1) Of note, thyroid was a common site, 9.3% of SM, in young WM female cohort. Cecum and most of brain cancers were noted among pts with old age at WM dx. Overall survival was poorest for LB. Conclusions: There was a 10% incidence of SM in WM survivors during 2000-2019. LB cancer carried worst OS among WM survivors and was the most prevalent, second to gender specific cancer, among patients with relatively younger onset WM. [Table: see text]